From owner-metabolic-reg@net.bio.net Mon Jan 05 22:00:00 1998 Path: biosci!ggr.co.uk!gzz78923 From: gzz78923@ggr.co.uk Newsgroups: bionet.metabolic-reg Subject: New DBsolve version Date: 6 Jan 1998 12:39:07 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 5 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801062037.UAA00419@ukwsv7.ggr.co.uk> NNTP-Posting-Host: net.bio.net DBsolve: software for metabolic, enzymatic and receptor-ligand binding simulation. Version 4.05 contains receptor-ligand-binding example: simultaneous fitting to ODE equations, implicit and explicit algebraic functions. http://sirius.iteb.serpukhov.su/~igor/ From owner-metabolic-reg@net.bio.net Mon Jan 05 22:00:00 1998 Path: biosci!agate!howland.erols.net!news.maxwell.syr.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: "s.j.eaton" Newsgroups: bionet.metabolic-reg Subject: Osmolality Date: 6 Jan 1998 12:50:36 -0000 Lines: 11 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <68t9as$5l3@mserv1.dl.ac.uk> Reply-To: s.eaton@ich.ucl.ac.uk MIME-Version: 1.0 Original-To: btk-mca@dl.ac.uk Does anyone know the osmolality of creatine and creatine phosphate or could point me at a reference book that includes such things? Thank you Simon Eaton Simon Eaton Research Fellow, Unit of Paediatric Surgery Institute of Child Health 30 Guilford Street, London WC1N 1EH Phone +44 171 242 9789 ext. 2254/2247 Fax +44 171 404 6181 From owner-metabolic-reg@net.bio.net Wed Jan 07 22:00:00 1998 Path: biosci!daresbury!uninett.no!news.algonet.se!rill.news.pipex.net!pipex!dispose.news.demon.net!demon!news.demon.co.uk!demon!fssc.demon.co.uk!HSauro From: Herbert M Sauro Newsgroups: bionet.metabolic-reg Subject: ANNOUCEMENT: New Metabolic Simulation Software Date: Thu, 8 Jan 1998 19:31:35 +0000 Organization: Future Skill Software Distribution: world Message-ID: NNTP-Posting-Host: fssc.demon.co.uk X-NNTP-Posting-Host: fssc.demon.co.uk [194.222.57.39] MIME-Version: 1.0 X-Newsreader: Turnpike Version 1.12 Lines: 298 Date: December 1997 TALIS ---------------- Visual, interactive, real-time metabolic simulation ANNOUNCEMENT: TALIS - Metabolic/Chemical Simulation Software I am very pleased to announce the immediate availability of a beta version of a new metabolic simulation package for Windows 95, codename TALIS. Main Features (not all necessarily available in beta version) ------------- Talis has a number of unique features which will be of interest to readers of this group: 1) Talis is entirely graphical in nature, that is metabolic pathways are specified by drawing them on the screen using the mouse. 2) Talis offers live interaction with the simulated pathway. This means you can modify parameters (Km, Vmax etc.) as the simulation runs and observe the effect immediately. 3) Talis supports a number of so-called devices which allow specific live interactions with the pathway under study. 4) Talis exposes much of its core functionality through a Tools Service interface. This means anyone can write addon modules to enhance Talis' feature set. Examples with complete source will be available upon release of the final version. Availability ------------ Talis is available now in a (very) pre-release version (0.8v) and is freely available to all non-commerical application users. Commerical users are free to evaluate Talis but may not use Talis for commercial gain without express permission from the author (please read the licence agreement in the readme file). Talis is a Windows 95, 32 bit application, it has not been tested under Win NT. You will find the program both computationally and graphically very demanding on your computer hardware, I would therefore not recommend anything less than a 133MHz Pentium (although these days that's not much). I don't know what the memory requirements are but I am sure 8MB must be a minimum, the more the better - and it's not my fault. A pre-release beta version of Talis is available now for download from: http://www.fssc.demon.co.uk/Talis.htm The .htm extension is VERY important, you won't get to the web site without it. The WEB site is a bit thin on glitz so it's fairly basic. You can also get it directly from the metabolic software ftp archive at: ftp://bmsdarwin.brookes.ac.uk/pub/software/ibmpc/talis Install Talis by executing the self-installing archive, tsetup.exe Who is Talis aimed at? ---------------------- Version One of Talis is probably most suitable for introducing metabolic dynamics to students. In it's present form it lacks many of the features one would expect a full research package to offer, and also it not even finished. If you want a quick demonstration of what Talis can do then download it, install it, and run it. Open the pathway called brus1.pth. Click on the run button in the top right-hand corner of the screen and watch. Features -------- 1. The drawing area for Talis pathways is virtually unlimited. 2. There is no limit to the number of reactions, metabolites or devices in a single model. The only thing that will limit the size of your model is therefore hardware, there are no software limits. 3. Two types of metabolite are supported (*), floating and fixed boundary pools. In the full version metabolites will have two visual representations, either a simple name, e.g Fructose_6_Phosphate, or a pictogram, e.g a green blob. Only the name representation is fully implemented. There are a number of display characteristics of the metabolites which can be changed including vertical or horizontal mini-strips to display some state of the metabolite. If you've ever played command and conquer or some similar game then you'll know what I mean. (*) note: the term metabolite is used here in the general sense and includes both 'metabolites', proteins or any entity which can be represented by a concentration. 4. Four reactions types are currently supported (more will follow in later versions): UniUni, BiUni, UniBi and BiBi. Stoichiometries can however be freely modified, thus it is possible to model reactions such as 2X + Y --> 3X. The limitation to BiBi is therefore not that severe, the only reason for this limitation is simply the time required to write necessary coding. 5. Reactions rate laws can be specified either from a list of pre- defined laws or you can enter your own. 6. Reactions arcs are drawn using one or more bezier curves, these have selectable control handles for fine adjustment. 7. Any thing on the display canvas can be dragged around until you're happy with the arrangement. Almost everything has right-mouse or double click support. This later point is actually very important as you'll notice that the interface at start up appears quite minimal (this is intentional) and some functions can only be accessed via the right-mouse popup menus. 8. Talis supports three types of devices, note that all devices can work live: a. Snoopers b. Controllers c. Injectors In the current release the Injector series has not been implement, these will become available as Talis approaches it's full version specification. 9. Snoopers. As the name implies these devices can be used to display the current states of the pathway. Three types are currently available: a. Simple, light-weight displays, eg bar strips and flow meters (partially implemented) b. A more elaborate bar-chart for displaying multiple charts (not fully implmented) c. Graph display. (very partially implemented!) All snooper devices can display metabolite concentations, rates of change, fluxes or any combination expressed as an algebraic expression (e.g S1+S2'+S3/Km) 10. Controllers. These devices (only one kind available at the moment) can be used to control the values of model parameters. Thus you can attach a controller to an enzyme reaction and use it to control the amount of enzyme, a reaction's Km or a hill coefficient etc. In future releases further controller types will be become available to enable users to simulate experimental procedures (eg titration) 11. Injectors. Not yet implemented but when they are they will allow you to add or remove mass from floating metabolite pools. Injectors will be particuarly important for changing the mass in conserved moiety cycles. 12. Zoom and panning of the image. 13. Unlimited undo. What this means is if you accidently delete glycolysis, you can get it back with a Ctrl Z. 14. Export SCAMP files (Import to be done soon). 15. Other things which I've forgotten or are too minor to mention here. --------------------------- There is still much to be done to bring Talis up to its full release state but I think the current version has enough functionality to make it a useful addition to the growing list of available metabolic software. I also wanted to get something out by the end of Decemeber 1997 what ever state it was in. Things still to be implemented or completed: 1. Complete all devices, especially the Injectors. 2. New open-file dialog box with ability to preview pathways. 3. Include some addon example modules (with source), including a reporting addon, an alignment addon and a stoichiometry analysis addon. 4. Finalise the Tools Services interface - this will happen when I do the above. 5. Import SCAMP files. I can probably do the same for other simulators if I can get hold of their saved binary file formats. 6. Some sort of Help file. 7. Enhance the rate-law library with further built-ins and library management facility. 8. Visual indicators to show regulatory and signal pathways - if I can sort out a good algorithm - I think this is a must. 9. Elasticities for time simulation. 10. Control over the ODE integrator and ESPECIALLY initial condition management 11. Access to raw simulation data for hard copy etc 12. Others things I've forgotten for the moment. 13. Suggestions from interested parties. --------------------------------------------- Please note that the current release is NOT the final version, you will find many things not working or only partially implmeneted, the current release is definitely beta. There is much remaining work to do on the program. I've been tinkering with it for almost a year and a half now and rather than spend more time on it (which is very little at the best of times) I've decided to distribute a pre-release version now. Ccomments on usability and especially reports of bugs (!) will be much appreciated - you may *even* find the program useful! If you do find a bug then it is vital that you describe EXACTLY how you generated it because if you want a fix then I need to be able to reproduce it on my own machine. Bear in mind that no one has seen this program before other myself so I'm probably in for many surprises and criticisms of interface design - but that's one reason why I'm releasing it early for. There are going to be some pretty obvious bugs and ommisions on first release, some of these I am aware of already but report what ever you find. Talis is a large and internally a very complex piece of software and there are bound to be problems and interface inconsistencies. One thing to bear in mind is that as I release updates I cannot guarantee that the binary format of saved pathway files will remain the same from revision to revision. I have build some redundancy into the saved format to try to mitigate this problem, at this easrly stage I am sure I will have to change the binary format of saved files. You can however export your models as SCAMP files which you'll be able to import later on no matter what version of Talis you have - so it's not quite the end of the world. I have no plans to charge for Talis. Version Two will commence once I've completed v1.0. The second version will basically add all the metabolic control analysis support, so roll on version One. Have fun. Herbert Sauro December 1997 Comments, suggestions etc. to HSauro@fssc.demon.co.uk The idea for Talis is something that has been on my mind for a long time but I would like thank Dennis Bray for his interest and encouragement in actually getting me started on this project a year and a half ago. I would also of course like to thank the UK Science Funding establishment for their foresight, their immense generousity and unwavering support, without which this project would never have got this far - ok, I lie, that last sentence is not quite true. ------------------------------------------------------------------------ Permanent Address: Herbert Sauro Penrodyn Pontrhydygroes Ystrad Meurig Ceredigion United Kingdom SY25 6DP Current location (until May 98): Herbert Sauro 2F3, 19 Yeaman Place Polwarth Edinburgh Scotland EH11 1BS Tel: 0131 229 3383 (evenings); 0131 220 3993 (day time) Permanent email: HSauro@fssc.demon.co.uk -- Herbert M Sauro email: HSauro@fssc.demon.co.uk Telephone: 01974 282428 ----------------------------------------------------------------------- "He who cannot draw on 3000 years is living from hand to mouth" Goethe "Ah, but a man's reach should exceed his grasp, or what's a heaven for?" R Browning. From owner-metabolic-reg@net.bio.net Wed Jan 07 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: "Richard L. Veech" <75031.62@compuserve.com> (by way of David Fell ) Newsgroups: bionet.metabolic-reg Subject: Automation of MCA - post vacant Date: 8 Jan 1998 18:14:20 -0000 Lines: 42 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <69351s$9qh@mserv1.dl.ac.uk> X-Sender: david@bmshuxley.brookes.ac.uk Original-To: btk-mca@dl.ac.uk, pedro@bmshuxley.brookes.ac.uk Message from David Fell: The message that follows was one I received from Dr Richard Veech, who works at the National Institute for Alcoholism & Alcohol Abuse, Bethesda. At my suggestion, he agreed to its being posted on this newsgroup. Reply directly to him if interested - he is not a reader of this group. ============================================================== It strikes me that the reasons there are so few bottom up control strenght studies is that the work required is simply to massive. It took us nearly 3 years and a number of people to produce the Kashiwaya paper. * Nevertheless, one might derive useful information from such studies involving other hormones, drugs, diets or genetic states. Accordingly I have decided to attempt to automate the analyses the metabolite and kinetic assays necessary to perform such analyses. Of necessity this will also require a large amount of data manipulation, quality controls and summarization. Standard biochemical training is probably not what is required, but rather experience in physics and or computer science and automation. We have available a fellowship which initially pays $29,000/yr renewable for up to 5 years with increases. Would you know any qualified candidates who might be interested in such a project under these terms? Dr Richard Veech (Note: * J. Biol. Chem. 269, 25502-14 (1994)) =============================================================== When I suggested he put it on this noticeboard, pointing out that there may be readers who combined the biochemical and computing experties, he replied: "I would appreciate you putting an announcement on your btk-mca newsgroup to see if anyone is interested. We are at a point now where very few people are capable of doing precise metabolite assays and evaluation of kinetic constants. Our problem is to try to turn hand crafted expertese into automated proceedures. That presents a number of engineering difficulties, but I would think that, given the automated clinical machines available, the bulk of the problem will involve transferring and manipulating data, and building in checks on its reliability." From owner-metabolic-reg@net.bio.net Thu Jan 08 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: David Fell Newsgroups: bionet.metabolic-reg Subject: Re: Talis Date: 9 Jan 1998 10:13:02 -0000 Lines: 14 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <694t7e$p1i@mserv1.dl.ac.uk> X-Sender: david@bmshuxley.brookes.ac.uk Original-To: btk-mca@dl.ac.uk Apologies to anyone who didn't succeed in getting Talis from bmsdarwin following Herbert's announcement. There was a short delay before the files were installed. However, they are there now. My recommendation: get it now and take a look - it's really impressive. David ========================================================= David Fell, School of Biological & Molecular Sciences, Oxford Brookes University, Oxford OX3 0BP, UK Tel. +44 (0)1865 483247 FAX +44 (0)1865 484017 daf@bms.brookes.ac.uk http://www.brookes.ac.uk/bms/research/molcell/fell/fell.html From owner-metabolic-reg@net.bio.net Sat Jan 10 22:00:00 1998 Path: biosci!MCS.ANL.GOV!goryanin From: goryanin@MCS.ANL.GOV (Igor Goryanin) Newsgroups: bionet.metabolic-reg Subject: (none) Date: 11 Jan 1998 06:20:38 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 5 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801111419.IAA07938@juju> NNTP-Posting-Host: net.bio.net DBsolve site has been moved DBsolve: software for metabolic, enzymatic and receptor-ligand binding simulation site has been moved to US. http://www.mcs.anl.gov/home/compbio/Goryanin/ Please, do not try to visit site in Russia. From owner-metabolic-reg@net.bio.net Tue Jan 13 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: vExplorer for Macintosh Date: 14 Jan 1998 05:08:27 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 43 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net A year or so ago Herbert Sauro posted a message about a utility called vExplorer that he wrote for graphical exploration of the properties of mathematical functions. It was (and is) available from the BTK-MCA FTP site in Oxford. I found this a very nice little program, as did others who commented on it on this news group. However, from my point of view it had the serious disadvantage of being a Windows program so I had to switch on my PC in order to run it, and I wrote a program to do this same thing on the Macintosh. This is (with Herbert's permission) also called vExplorer and is now available from the BTK-MCA FTP site at ftp://bmsdarwin.brookes.ac.uk/pub/software/mac/explorer/. There is a web page describing it (with a screen shot) at http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/vexpl.htm. Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm ================================================================ Athel Cornish-Bowden Laboratoire de Chimie Bacterienne, Centre National de la Recherche Scientifique, 31 chemin Joseph-Aiguier, B.P. 71, 13402 Marseille Cedex 20, France Phone: + 33 491 16 41 38; fax: + 33 491 71 89 14 ****Email: If you have had trouble with my alternative address at bigfoot.com, please use athel@ibsm.cnrs-mrs.fr instead. Even if you have not had problems I intend to phase out the bigfoot address (though without cancelling it, so if it has worked before it should continue to do so) Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm From owner-metabolic-reg@net.bio.net Tue Jan 20 22:00:00 1998 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.metabolic-reg Subject: BIOSCI/bionet miniFAQ & Fundraiser Date: 21 Jan 1998 02:00:05 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 233 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801211000.CAA00744@net.bio.net> NNTP-Posting-Host: net.bio.net (LAST REVISION: 30-JUL-95) This BIOSCI "miniFAQ" is designed to answer the questions that come up the *most frequently*. The main BIOSCI FAQ (Frequently Asked Questions) is accessible on the World Wide Web at URL http://www.bio.net/. If you can not find an answer to your question in this or other documentation, the BIOSCI technical support staff answers e-mail queries sent to biosci-help@net.bio.net We can only answer questions about the use of the newsgroups and mailing lists. We unfortunately do not have the staff to do Internet information searches or answer scientific questions. Please post those to the appropriate BIOSCI/bionet newsgroups. Contents: -------- 0) BIOSCI NEEDS YOUR SUPPORT!! 1) Using the WWW to access the BIOSCI/bionet newsgroups. 2) What to do about "spams," i.e., junk mail, ads, etc. 3) Examples of subscribing and unsubscribing to the mailing lists. 4) The BIOSCI user address and research interest directory. 0) BIOSCI NEEDS YOUR SUPPORT!! ------------------------------ BIOSCI's government funding has been expended, and we are now operating solely from advertising revenue that we have raised from our Web site at http://www.bio.net/. We need just a few minutes of your time to help us serve you. You can do two important things which will take very little time for you individually and will immensely help us continue to help you. First, please use our WWW system at http://www.bio.net/ to access the archives. You can post or reply to messages via your Web browser as described in item #1 below. Your usage helps attract sponsors. If you contact any of our sponsors, please be sure to thank them for supporting BIOSCI. It is critical for them to get this feedback if they are to continue their sponsorship for the long term. Second, if you work for a company or organization that provides products or services of interest to the biology community, please pass this message on to your marketing or marketing communications department or other appropriate group. Please ask them to help support BIOSCI by sponsoring our Web site and explain the uses and benefits of the system to the biology community. If they are interested, they can then contact us for further information at our tech support address, biosci-help@net.bio.net. 1) Using the WWW to access the BIOSCI/bionet newsgroups. -------------------------------------------------------- As of 10 December 1995, all BIOSCI/bionet full newsgroups are accessible through the World Wide Web (WWW) at URL http://www.bio.net. One can read and reply publicly or privately to both recent postings and archived messages through one's Web browser if it is configured properly to send e-mail. Each newsgroup is equipped with its own WAIS index. 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Below we give an example utilizing the METHODS-AND-REAGENTS list at both of our two BIOSCI sites: Users in the Americas and Pacific Rim countries who use the BIOSCI ------------------------------------------------------------------ node at computer net.bio.net: ---------------------------- A) Determine the "listname" which is the <=8 character mail address ^^^^^^^^^^^^^ for the group. These can be found in the BIOSCI Info. Sheet. For the METHODS-AND-REAGENTS group the mailing address is methods@net.bio.net. The listname is the portion of the address to the left of the @ sign, i.e., "methods". The listname is used with the "subscribe" and "unsubscribe" commands illustrated below. B) Mail all commands in the body of a mail message addressed to biosci-server@net.bio.net. Do NOT send commands to the newsgroup posting addresses! Leave the Subject: line blank, any text on it will be ignored. 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From owner-metabolic-reg@net.bio.net Wed Jan 21 22:00:00 1998 Path: biosci!agate!howland.erols.net!news.maxwell.syr.edu!news.cis.ohio-state.edu!magnus.acs.ohio-state.edu!smtp.service.ohio-state.edu!rdisilvexx From: rdisilvexx@smtp.service.ohio-state.edu (Robert DiSilvestro) Newsgroups: bionet.metabolic-reg Subject: Raidoactive Cr alternatives? Date: Thu, 22 Jan 1998 15:32:08 GMT Organization: The Ohio State University Lines: 6 Message-ID: NNTP-Posting-Host: 140.254.42.101 X-Newsreader: Trumpet for Windows [Version 1.0 Rev B final beta #4] This group doesn't seem to get much attention, so, I don't know who will see this. I'll try anyway. Does anyone know of a nonradioactive alternative to using hot Cr to follow efflux patterns? I know I have seen this in ads, but I can't remember where. To E-mail me, remove the x's from my name. From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: You don't have to understand it? Date: 23 Jan 1998 07:07:02 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 41 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net In the most recent issue of Proc. Natl. Acad. Sci. USA that I have seen (vol. 94, pp. 13388-13389 (1997)), Roy Pollock and Michael Gilman deliver themselves of the following opinion: "One of the beautiful things about biology is that you don't have to fully understand it to put it to good use. The engineers who design spacecraft may need a certain working familiarity with all of the parts in their systems. But biologists, and particularly biologists whose mission is to treat human disease, can make do with considerably more ignorance. One reason for this difference is that biological control is usually exerted through linear pathways of protein-protein interactions. Intervention at a single known point in the pathway often is sufficient to capture that pathway in its entirety." Even if we ignore the false analogy between creating a new spacecraft with modifying an existing biological system (which is easier: altering the trajectory of a rocket already in flight, or designing a new biological system from scratch? Can we conclude from the answer that biology is more demanding than rocket science? Or is it just a silly comparison to start off with?), and even if we recognize that they are not using the term pathway in the sense of metabolic pathway, this remains a worrying opinion. Is there any sense in which we can safely say "Intervention at a single known point in the pathway often is sufficient to capture that pathway in its entirety"? Certainly Henrik Kacser wouldn't have agreed -- his view that the only way to understand systems is to study systems was a lot more general than just metabolic pathways. What do readers of this news group think? Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 23 Jan 1998 07:33:49 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 8 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <1326571619-228771521@ciit.org> NNTP-Posting-Host: net.bio.net There seem to be intermittent periods of high (useful) activity, and it mat be worthwile keeping around for when those occur. So what if it's quite for long spells? -Paul Schlosser From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: This group doesn't seem to get much attention Date: 23 Jan 1998 07:16:26 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 19 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Robert DiSilvestro wrote: >This group doesn't seem to get much attention, so, I don't know who will >see this. I'll try anyway... True, alas. Do we want this group to continue, or shall we allow it to die a natural death? Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!newsfeeds.sol.net!nntp.inc.net!paperboy01.iconnet.net!news.mcleodusa.net!news From: "Andrew R. Apel" Newsgroups: bionet.metabolic-reg Subject: Excerpt From AgBiotech Reporter - Call For Submissions Date: Fri, 23 Jan 1998 10:29:37 -0600 Organization: McleodUSA - http://www.mcleodusa.net Lines: 57 Message-ID: <34C8C570.7B74A10F@mcleodusa.net> NNTP-Posting-Host: 210-A-35-210.ppp.mcleodusa.net Mime-Version: 1.0 Content-Type: multipart/mixed; boundary="------------234565B9CCD474737D85FA1C" X-Mailer: Mozilla 4.02 [en]C-DIAL (Win95; U) This is a multi-part message in MIME format. --------------234565B9CCD474737D85FA1C Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit --------------234565B9CCD474737D85FA1C Content-Type: text/html; charset=us-ascii; name="notice.htm" Content-Transfer-Encoding: 7bit Content-Disposition: inline; filename="notice.htm" Content-Base: "file:///A|/notice.htm"  

A Letter To Our Readers

by Andrew Apel
Managing Editor

The staff of AgBiotech Reporter have long held to a philosophy of introducing incremental changes as a means to improve this publication, and from talking to a number of our readers, we've found our approach has met with a good deal of approval. This edition introduces yet another incremental change, which we hope will be similarly well-received.

Recently, we took another (customary) hard look at the way we cover the news and noticed that most of the scientific data which circulate in the field of agricultural biotechnology deal with discoveries which represent substantial advances over prior art and often lead to the formation of new intellectual properties or products. Beyond a doubt, that information is interesting--but little is available about the demanding and intricate work of the professional scientist that precedes such discoveries. Perhaps worse than this, from a practical standpoint, is the lack of information on those incremental improvements in technique or procedure which are unspectacular, but nonetheless useful or productive in the lab.

To make up for this unfortunate lacuna, we have added a "Tips and Techniques" section in Research News, where scientists can exchange information of this nature, with each other. It is my personal hope that the readers of AgBiotech Reporter will come to view this new section as theirs, and to treat it as a means of helping their colleagues around the world to more efficiently achieve the results they are looking for. We are grateful to Dr. Altosaar for the offering which has inaugurated our new section, and look forward to receiving more in the same vein at fax (319) 277-3783, email A.Apel@mcleodusa.net. --------------234565B9CCD474737D85FA1C-- From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!VALIANT.NIEHS.NIH.GOV!kohn From: kohn@VALIANT.NIEHS.NIH.GOV ("Michael Kohn") Newsgroups: bionet.metabolic-reg Subject: Re: You don't have to understand it? Date: 23 Jan 1998 08:11:39 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 43 Sender: daemon@net.bio.net Distribution: world Message-ID: <9801231103.ZM19755@valiant.niehs.nih.gov> NNTP-Posting-Host: net.bio.net > In the most recent issue of Proc. Natl. Acad. Sci. USA that I have seen > (vol. 94, pp. 13388-13389 (1997)), Roy Pollock and Michael Gilman deliver > themselves of the following opinion: ... This opinion is so preposterous that it almost deserves no notice except that it is so pervasive among biologists that it must be fought and ultimately (one hopes) extirpated. If limited information is adequate for treatment of disease, why has it been so difficult to treat AIDS? We know the genetic sequence of the virus and the proteins encoded. We understand the proteolytic processing of the genetic transcript. We know the identity of the target cells and the receptors required for viral entry. And yet nothing we try is any more than a temporary palliative. Biochemical pathways are not "linear pathways of protein-protein interactions." They are full of feedback loops caused by shared cofactors and activation or inhibition by metabolic intermediates produced remote in the pathway from their sites of action. Many enzymes exhibit highly nonlinear kinetics or cooperative effects of ligands, leading to responses of the entire pathway that are not proportionsal to a given perturbation. How then can "[i]ntervention at a single known point in the pathway often [be] sufficient to capture that pathway in its entirety"? SHOW ME THE EVIDENCE. This kind of hand-waving is the antithesis of science. "The only way to understand systems is to study systems." Engrave it on the lintels of your doorways. -- Michael C. Kohn Laboratory of Computational Biology and Risk Analysis National Institute of Environmental Health Sciences P.O. Box 12233, Mail Drop A3-06 Research Triangle Park, NC 27709-2233 Telephone: 919-541-4929 (voice) 919-541-1479 (fax) e-mail: kohn@valiant.niehs.nih.gov WWW home page: http://valiant.niehs.nih.gov From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: You don't have to understand it? Date: 23 Jan 1998 07:44:54 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 24 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <1326572464-228720699@ciit.org> NNTP-Posting-Host: net.bio.net >The engineers who design spacecraft may need a certain working >familiarity with all of the parts in their systems. But biologists, >and particularly biologists whose mission is to treat human disease, >can make do with considerably more ignorance. It seems to me that this is "relative" knowledge. It is possible for an engineer to have a working familiarity with all the parts in their systems. But the same "quantity" of knowledge represents only a fraction of what goes on in biology. In fact one *cannot* have a working familiarity with all parts of biology because there are still plenty of things that are simply unknown. It is true that a lot can be (is) done with only a partial knowledge of biology (despite the demonstrate ignorance of the complexity of regulation). But to me that is more analagous to the astronaut, who is capable of navigating a spacecraft, even if he or she doesn't know exactly how every microprocessor in every instrument functions. The quoted statements indicate the mentality of an "astronaut", rather than that of an "engineer". -Paul From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!newsfeed.internetmci.com!131.103.1.116!news2.chicago.iagnet.net!iagnet.net!144.92.88.12!newsspool.doit.wisc.edu!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: You don't have to understand it? Date: Fri, 23 Jan 1998 15:02:41 -0600 Organization: BioKin Consulting Lines: 33 Message-ID: <34C90571.2C480C24@biokin.com> References: <9801231103.ZM19755@valiant.niehs.nih.gov> NNTP-Posting-Host: a8-39.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Michael Kohn wrote: > > > In the most recent issue of Proc. Natl. Acad. Sci. USA that I have seen > > (vol. 94, pp. 13388-13389 (1997)), Roy Pollock and Michael Gilman deliver > > themselves of the following opinion: ... > > This opinion is so preposterous that it almost deserves no notice In my own opinion, the manuscript review process in P.N.A.S. differs from other journals in such a way that it increases the likelihood of substandard work being published. As we all know, each manuscript must be (in essence) 'recommended' by a member of the Academy. Could it be that this procedure creates a reluctance on the part of some reviewers to reject a preposterous piece? Over the years, I collected several P.N.A.S. "gems" which are not only debatable but ridiculously pseudo-scientific both in style and contents, despite (or because?) they were 'recommended' by powerful personalities in contemporary American science. On the more general level, let us not kid ourselves about the nature of the scientific enterprise, so eloquently exposed by the philosopher Steven Fuller (University of Colorado, Department of Philosophy) in his book "Philosophy of Science and its Discontents". Established principles are frequently ignored in the published literature! As Fuller explains, preposterous opinions are par for the course, because of numerous reasons both intrinsic and extrinsic to the process of knowledge creation. However, I heartily agree with Michael Kohn: > [they] must be fought and ultimately (one hopes) extirpated _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!dispose.news.demon.net!demon!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: David Fell Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 23 Jan 1998 17:08:52 -0000 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aair4$7l1@mserv1.dl.ac.uk> X-Sender: david@bmshuxley.brookes.ac.uk Original-To: btk-mca@dl.ac.uk Lines: 33 Athel wrote: >Do we want this group to continue, or shall we allow it to die a natural death? > No need to get too despondent. Not all the activity provoked by the group appears on these pages. For example, following the announcement of the test version of the Talis simulation software available at our ftp site, there have been at about 8 downloads of the software. A similar number of downloads of Athel's Mac version of vExplorer have occurred, and one or two downloads of the PC version. Thus there are people out there who found those two messages of interest, even if they haven't posted an opinion of the software after getting it. One thing that has reduced is the amount of spam; restrictions recently imposed by commercial internet service providers and universities on access to their mailer demons have been partly successful in choking off some of the anonymous bulk mailings. Thus there's less to read here, but more of it is relevant. Another factor for those of us who teach is that this is a busy time of the year, which is why I'm signing off...... David ========================================================= David Fell, School of Biological & Molecular Sciences, Oxford Brookes University, Oxford OX3 0BP, UK Tel. +44 (0)1865 483247 FAX +44 (0)1865 484017 daf@bms.brookes.ac.uk http://www.brookes.ac.uk/bms/research/molcell/fell/fell.html From owner-metabolic-reg@net.bio.net Thu Jan 22 22:00:00 1998 Path: biosci!agate!newsgate.duke.edu!solaris.cc.vt.edu!fci-se!fci!news-feed.inet.tele.dk!bofh.vszbr.cz!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: "s.j.eaton" Newsgroups: bionet.metabolic-reg Subject: Keep the group going! Date: 23 Jan 1998 16:42:45 -0000 Lines: 11 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aaha5$5so@mserv1.dl.ac.uk> Reply-To: s.eaton@ich.ucl.ac.uk MIME-Version: 1.0 Original-To: btk-mca@dl.ac.uk I for one would vote in favour of keeping BTK-MCA continuing; I don't think it is dying a death but rather becoming more focussed- we have flurries of activity, plus generally useful notices fot software etc. Compare this to about 1 year ago when it was all xxx-nude or chain letter adverts. I know we still get them, but not as often... Simon Eaton Research Fellow, Unit of Paediatric Surgery Institute of Child Health 30 Guilford Street, London WC1N 1EH Phone +44 171 242 9789 ext. 2254/2247 Fax +44 171 404 6181 From owner-metabolic-reg@net.bio.net Fri Jan 23 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Chemical work Date: 24 Jan 1998 12:27:54 -0000 Lines: 46 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6acmoa$qpk@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk There is a paradox - this group is "thermodynamic" by definition and yet it is reluctant to discuss thermodynamic problems. Perhaps the way I set them some time ago was not perfect, but was that important? Does biothermodynamics contain no problems? Why has nobody else started a more fruitful discussion? Let me try again - I hope I can be more convincing now. The most basic definition of chemical (useful) work is given by the first law of thermodynamics: delta H = Qabs - Wu /1/ where delta H is the enthalpy of a chemical reaction, Qabs is the heat absorbed and Wu is the chemical work extracted from the reaction. Let us consider the EXOTHERMIC reaction A -> B /2/ If it is not coupled to another reaction, conversion of one mole A into B would just release heat equal to -(delta H). However if /2/ is coupled to another reaction, some of the energy released (-delta H) could be transfered to the other chemical system in the form of Wu, and the rest would still be dissipated as heat (Qabs, which is negative in this case). This is what /1/ says: the energy released by one mole of A is either entirely dissipated as heat (delta H) or, if the reaction is coupled, some of it is transfered as chemical work (Wu). Please let me know if this balance sounds plausible. If yes, we would go further to show that the other definition of chemical work: -Wu = delta G = delta Go + RTln((B)/(A)) /3/ is incompatible with it. What I was not able to explain before is that /3/ is in principle correct but it corresponds to a different PHYSICAL course of the reaction - in the first case Wu comes from the INTRAMOLECULAR energy of A, whereas /3/ corresponds to a special course in which the intramolecular energy does not matter - heat is absorbed from the environment and converted into Wu. For the ATP system, /3/ remains a definition of potential useful work done under reversible conditions, but only if this special course of the reaction takes place. It never does. The implications are incredible. Best regards, Pentcho Valev From owner-metabolic-reg@net.bio.net Fri Jan 23 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Chemical work Date: 24 Jan 1998 12:28:44 -0000 Lines: 46 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6acmps$qqm@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk There is a paradox - this group is "thermodynamic" by definition and yet it is reluctant to discuss thermodynamic problems. Perhaps the way I set them some time ago was not perfect, but was that important? Does biothermodynamics contain no problems? Why has nobody else started a more fruitful discussion? Let me try again - I hope I can be more convincing now. The most basic definition of chemical (useful) work is given by the first law of thermodynamics: delta H = Qabs - Wu /1/ where delta H is the enthalpy of a chemical reaction, Qabs is the heat absorbed and Wu is the chemical work extracted from the reaction. Let us consider the EXOTHERMIC reaction A -> B /2/ If it is not coupled to another reaction, conversion of one mole A into B would just release heat equal to -(delta H). However if /2/ is coupled to another reaction, some of the energy released (-delta H) could be transfered to the other chemical system in the form of Wu, and the rest would still be dissipated as heat (Qabs, which is negative in this case). This is what /1/ says: the energy released by one mole of A is either entirely dissipated as heat (delta H) or, if the reaction is coupled, some of it is transfered as chemical work (Wu). Please let me know if this balance sounds plausible. If yes, we would go further to show that the other definition of chemical work: -Wu = delta G = delta Go + RTln((B)/(A)) /3/ is incompatible with it. What I was not able to explain before is that /3/ is in principle correct but it corresponds to a different PHYSICAL course of the reaction - in the first case Wu comes from the INTRAMOLECULAR energy of A, whereas /3/ corresponds to a special course in which the intramolecular energy does not matter - heat is absorbed from the environment and converted into Wu. For the ATP system, /3/ remains a definition of potential useful work done under reversible conditions, but only if this special course of the reaction takes place. It never does. The implications are incredible. Best regards, Pentcho Valev From owner-metabolic-reg@net.bio.net Sat Jan 24 22:00:00 1998 Newsgroups: bionet.metabolic-reg Path: biosci!fcs280s.ncifcrf.gov!cpk-news-feed4.bbnplanet.com!cpk-news-feed1.bbnplanet.com!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!Cabal.CESspool!bofh.vszbr.cz!newsfeed2.uk.ibm.net!news.ibm.net.il!ibm.net!news.biu.ac.il!news.tau.ac.il!news.openu.ac.il!news From: hanan sela Subject: co enzayme q Content-Type: text/plain; charset=us-ascii Message-ID: <34CC4393.4893@telem.openu.ac.il> Sender: news@cs.openu.ac.il NNTP-Posting-Host: chanase.tppp.openu.ac.il Reply-To: chanase@telem.openu.ac.il Content-Transfer-Encoding: 7bit Organization: Open University of Israel - TELEM Project Mime-Version: 1.0 Date: Mon, 26 Jan 1998 08:04:35 GMT X-Mailer: Mozilla 3.02 (Win16; I) Lines: 3 i am searching for sientific information about coq10. explantions how it is functioning? what is the best vgetarian source of it? thank you. hanan sela From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: Re: Chemical work Date: 26 Jan 1998 00:45:06 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 38 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Pentcho Valev claimed: >There is a paradox - this group is "thermodynamic" by definition and yet >it is reluctant to discuss thermodynamic problems. I see no evidence for this supposed reluctance. If anyone raises a cogent point about biological thermodynamics I believe the readers of this group will be more than ready to discuss it. The points that Pentcho raised seven or eight months ago were discussed at very great length, and several regular contributors (I'm thinking especially of Guy Brown, but there were others) went to a lot of trouble to explain the errors in the purported paradoxes, but it was like arguing with a brick wall. There was a constant reliance on thought experiments even for matters where normal wet experiments were perfectly feasible. When -- eventually -- Pentcho was persuaded to do a wet experiment he found that it went the way his critics said it would go and not the way his cogitation had led him to expect. However, to judge from the latest contribution this doesn't seem to have convinced him that the problems are not with classical thermodynamics but with his understanding of it. It's perhaps worth pointing out that one half of the group's name refers to biological thermodynamics, not to thermodynamics in general. I don't see anything especially biological about the question now raised. Of course, I'm not saying that that non-biological questions in thermodynamics can't be raised, only that people whose primary interests are biological shouldn't feel particularly embarrassed about leaving them unanswered. Are there no groups on chemical thermodynamics for raising such questions? Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!agate!howland.erols.net!news.maxwell.syr.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Thermodynamic potential of the ATP system (reply to Athel) Date: 26 Jan 1998 11:44:49 -0000 Lines: 61 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6ahsvh$g0j@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Athel, I do not know how to reply to your personal attacks. Maybe I should only reply to your statement that what I am writing about has no biological significance. I think that it, if true, is quite significant. Let me develop the issue to some extent. The following idealised system can give us some rough physical picture of the two types of work that can be extracted from a chemical reaction - statistical suitably described by delta G and molecular suitably described by delta H. ------------------------------------------------------------------------- A <-> B (equilibrium) membrane-permeable-only-to-A////////////membrane-permeable-only-to-B////// A -> B (non-equilibrium) --------------------------------------------------------------------------- The reaction A -> B is at equilibrium in the container above, and not at equilibrium in the container below. Also, the concentration of A is greater below so that there is an upward transmembrane flux of A, whereas the concentration of B is greater in the equilibrium system so that there is a downward flux of B. Also, the reaction A -> B is EXOTHERMIC. As A and B cross the membrane, they can do OSMOTIC work. It is not difficult to see that, for one mole A going up and returning to the non-equilibrium system as B, the maximum osmotic work that can be obtained is the negative of delta G = delta Go + RTln((B)/(A)) /1/ On the other hand, as A is converted into B within the non-equilibrium system, the energy released in each elementary chemical act can be transfered to some other molecule in the form of MOLECULAR work. If it is not transfered, it will be dissipated as heat. At constant temperature and pressure, this heat is represented, at the macroscopic level, by the enthalpy of reaction. So the enthalpy gives the maximum work of this type. This work depends on the coupling mechanism (if it is not perfect, much of the energy is dissipated), but is independent of the concentrations and the distance from equilibrium. Now we can imagine the following isothermal cycle: one mole of A is converted into B in the non-equilibrium system but the reaction is perfectly coupled to another reaction so that the whole energy released is transfered to another system in the form of chemical work Wu = -(delta H). Then the mole of B is reversibly converted into A along the path crossing the equilibrium system. The osmotic work spent is equal to -(delta G). It is rather convenient now to think of a concrete system - the ATP system, which does some molecular work but is restored by an osmotic mechanism. In accordance with the above idealized scheme, we can call the maximum chemical work gained as the system undergoes a cycle "thermodynamic potential of the ATP system". It is Pt = -(delta H - delta G) /2/ I hope you would agree that this result is quite relevant to biological systems. But it might prove wrong - please direct your attention towards this aspect - everything else, including my personal flaws and earlier mistakes, is immaterial. Best regards, Pentcho From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!agate!ihnp4.ucsd.edu!sdd.hp.com!usc!howland.erols.net!newsxfer3.itd.umich.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Nightmare (reply to Athel) Date: 26 Jan 1998 17:11:14 -0000 Lines: 5 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aig3i$4s8@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Athel, I do not want to be a nightmare (at least so I feel). Of course I will give up - sorry for posting - you can be absolutely sure that this will never happen again in this ng. Pentcho From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!agate!newsgate.duke.edu!news.ysu.edu!Cabal.CESspool!bofh.vszbr.cz!news.maxwell.syr.edu!news.cis.ohio-state.edu!magnus.acs.ohio-state.edu!smtp.service.ohio-state.edu!rdisilvexx From: rdisilvexx@smtp.service.ohio-state.edu (Robert DiSilvestro) Newsgroups: bionet.metabolic-reg Subject: Thanks, but how about the question Date: Mon, 26 Jan 1998 22:15:24 GMT Organization: The Ohio State University Lines: 6 Message-ID: NNTP-Posting-Host: 140.254.42.101 X-Newsreader: Trumpet for Windows [Version 1.0 Rev B final beta #4] I appreciate all the response I got about the group not getting much use. However, nobody addressed my actual question. Does anyone know about a nonradioactive alternative to Cr isotope for looking at cell fluxes? I know there is one, but I forget what it is or who makes the needed reagents. To E-mail me remove the x's. From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!newsfeed.internetmci.com!204.59.152.222!news-peer.gip.net!news.gsl.net!gip.net!sunqbc.risq.qc.ca!rcogate.rco.qc.ca!altitude!usenet From: "Achim Recktenwald, Ph.D." Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: Mon, 26 Jan 1998 14:53:22 -0500 Organization: CAM Lines: 35 Message-ID: <34CCE9B1.3FBE3FD0@ibex.ca> References: Reply-To: reckteac@ibex.ca NNTP-Posting-Host: ibex.hip.cam.org Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.04 [en] (Win95; I) Athel Cornish-Bowden wrote: > Robert DiSilvestro wrote: > > >This group doesn't seem to get much attention, so, I don't know who will > >see this. I'll try anyway... > > True, alas. > > Do we want this group to continue, or shall we allow it to die a natural death? > > Athel Please, continue. This is the only group, where it is possible to post questions to enzyme kinetic problems. At least the only one with a reasonable chance to get a correct answer. Achim __________________________ Achim Recktenwald, PhD IBEX Technologies, Inc. 5485 rue Pare Montreal, Quebec, H4P 1P7 Canada Fax : (514) 344-8827 email: reckteac@ibex.ca The usual disclaimers apply. From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!ATHE.WUSTL.EDU!toni From: toni@ATHE.WUSTL.EDU (Toni Kazic) Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 26 Jan 1998 10:59:43 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 12 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801261857.MAA05275@athe.wustl.edu> References: <6aair4$7l1@mserv1.dl.ac.uk> NNTP-Posting-Host: net.bio.net good heavens, yes, continue. The signal/noise is unusually high, and silence is not a problem. Toni Toni Kazic Institute for Biomedical Computing Washington University toni@athe.wustl.edu http://ibc.wustl.edu/~toni From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Formalism (reply to Igor Plesner) Date: 26 Jan 1998 13:25:25 -0000 Lines: 35 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6ai2s5$lo4@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Hi, Igor. Nice to hear from you again. Please do not be offended, but I find your way of thinking too formal - you are usually right but about insignificant matters which I see as obvious and do not pay them much attention. For instance, you wrote:>>>>>>>>>>>>> Dear Pencho: How can you expect people to discuss with you when all your premises are wrong? Your formula 1 is neither the first law of thermodynamics, nor is it ' the most basic definition of chemical work'. What happened to all other types of work, such as electrical work, work by gravity, magnetic work etc.? How is it apparent from /1/ that delta H is the heat absorbed AT CONSTANT PRESSURE? Likewise, your formula /3/ is - assuming that you remember to put activities for (A) and (B) - an expression for the MAXIMUM (i.e.REVERSIBLE!) CHEMICAL WORK OBTAINABLE AT CONSTANT TERMPERATURE AND PRESSURE. Note the word 'reversible'. This is all texbook stuff | <<<<<<<<<<<<< Please believe me that there is nothing in your text above that I do not know. Of course formula 1 is not the first law, but it is derived from the first law in the following way: delta H = delta U + P(delta V) = Qabs - Wu - P(delta V) + P(delta V) /1/ There are people for which /1/ is obvious - please become one of them. Wu is USEFUL work - CHEMICAL is just synonymous. Delta H is not always the heat absorbed at constant pressure - only when NO USEFUL WORK IS DONE. I would not forget to put activities in /3/, but in this case this is immaterial - it is even better to assume that all solutions are ideal and activities and concentrations coincide. Also, I do know that the work represented by /3/ is reversible. Igor, it would be nice for us to put the physical picture before formal definitions (of course, without ignoring them). Believe me, this creates problems, but on the other hand is the only way of developing science. Best regards, Pentcho From owner-metabolic-reg@net.bio.net Sun Jan 25 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: Re: Thermodynamic potential of the ATP system (reply to Athel) Date: 26 Jan 1998 07:34:03 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 49 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Pentcho Valev wrote: >Athel, I do not know how to reply to your personal attacks. What personal attacks? I only wanted to remind readers of this group (and inform those who have joined since last August), that during the period June-September 1997 there were approximately two messages per day either from Pentcho or from other people trying to deal with the points he raised (not to mention a similar abundance of similar exchanges in other news groups). For him to come back now, after describing his own contributions to this group in the following words: >I agree with Pedro Mendes that a lot of rubish has been thrown out of my >computer (Pentcho Valev in >http://www.bio.net/hypermail/BTK-MCA/9709/0023.html) with the claim that there is a lack of interest in discussing thermodynamic questions takes a lot of nerve. In that message he continued: >I do not think that this should continue, so I would like to apologise to >the group and promise not to contribute any more. In the present message, he continues: >Maybe I should only reply to your statement that what I am writing about >has no biological significance. I think that it, if true, is quite >significant. The crucial words are "if true". In any case, Pentcho is "replying" to a "statement" that I did not make. There was no statement in my message to the effect that Pentcho's new point had no biological significance, only that there was nothing *especially* biological about it. Of course it is true that if classical thermodynamics turns out to be all wrong then this will have biological implications, but I still think it would be more useful to get the chemistry right first and worry about the biological implications afterwards. Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Elisabeth Bull Daae Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 27 Jan 1998 12:24:29 -0000 Lines: 30 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6akjlt$p9@mserv1.dl.ac.uk> X-Sender: ucecebu@pop-server.bcc.ac.uk Original-To: btk-mca@dl.ac.uk I would just like to add my name to the list of people who think this group is worth continuing. I completely agree with Achim Recktenwald who wrote : " This is the only group, where it is possible to post questions to enzyme kinetic problems. At least the only one with a reasonable chance to get a correct answer." It has also have been pointed out that the group is an excellent place to find info on updated and relevant software. And I am sure there are quite a few people out there like me who are reasonably new to the field of metabolic regulation etc. and enjoys reading and learning from discussions and comments by more experienced people. It does not matter if it is quiet for some months. It is actually good that we don't have to much activity, because when you get a mail from this group once in a while you actually read it. If it was long postings every day, it would quickly become overwhelming and it would not be time to read all of it. Quality is always better than quantity! Let the group live! Elisabeth ----------------------------------------------- Elisabeth B. Daae The Advanced Centre for Biochemical Engineering University College London Torrington Place London WC1E 7JE, UK From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 27 Jan 1998 11:42:03 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 37 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <1326212041-250399119@ciit.org> NNTP-Posting-Host: net.bio.net >From: Herbert M Sauro >In a mixed solution containing two components, A and B and an enzyme >which can convert A + B to C, the rate at which the enzyme complex >EAB forms is proportional to E*A*B - I hope I've got that bit right. That's assuming that all three must collide at once to form the complex, which I don't think is typically the case. What you should consider is the sequence of elementary steps: A + E -> A*E or B + E -> B*E then A*E + B -> A*B*E or B*E + A -> A*B*E This is because the enzyme is capable of binding one substrate and holding onto it while waiting for the second. In some cases (I think) the order of binding is specific, while in others you can bind either A or B first. With certain simplifying assumptions you may be able to show that this is approximated by E*A*B, but I'm not sure of that. >What I want to know is what would happen if the enzyme were stuck on >a membrane, i.e confined to a 2D surface but with the substrates, >A + B still mixed in the bulk solution. ... Here the concentration of E becomes defined as per unit surface area rather than per unit volume, but the form of the rate equation remains the same. This is because it still matters how much enzyme is on the membrane: if you have 100 molecules/mm^2 you would expect a reaction rate 10 times faster than if you have 10 molecules/mm^2, given the same total surface area of membrane and the same concentration of A and B in the adjacent medium. -Paul Schlosser From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!bloom-beacon.mit.edu!news.kodak.com!news-pen-16.sprintlink.net!newsfeed.nysernet.net!news.nysernet.net!207.41.200.14!news-pen-14.sprintlink.net!206.229.87.26!news-east.sprintlink.net!news-peer.sprintlink.net!news.sprintlink.net!Sprint!news-peer.gip.net!news.gsl.net!gip.net!news.idt.net!dispose.news.demon.net!demon!news.demon.co.uk!demon!fssc.demon.co.uk!HSauro From: Herbert M Sauro Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: Tue, 27 Jan 1998 19:10:42 +0000 Distribution: bionet Message-ID: References: <6akjlt$p9@mserv1.dl.ac.uk> NNTP-Posting-Host: fssc.demon.co.uk X-NNTP-Posting-Host: fssc.demon.co.uk [194.222.57.39] MIME-Version: 1.0 X-Newsreader: Turnpike Version 3.02 Lines: 26 Of course keep the newsgroup going....and here's a question for its readers: I don't have easy access to University libraries etc because if I did I could probably look it up but my question concerns membrane transport kinetics. In a mixed solution containing two components, A and B and an enzyme which can convert A + B to C, the rate at which the enzyme complex EAB forms is proportional to E*A*B - I hope I've got that bit right. I presume this comes from considerations of collision probabilities in a perfectly mixed compartment. What I want to know is what would happen if the enzyme were stuck on a membrane, i.e confined to a 2D surface but with the substrates, A + B still mixed in the bulk solution. What would be the rate of formation of EAB be proportional too? Would it be the same (i.e E*A*B) or different because one of the colliding particles (E) can no longer freely diffuse in 3D? Herbert Sauro -- Herbert M Sauro email: HSauro@fssc.demon.co.uk Telephone: 0131 229 3383 ----------------------------------------------------------------------- "He who cannot draw on 3000 years is living from hand to mouth" Goethe "Ah, but a man's reach should exceed his grasp, or what's a heaven for?" R Browning. From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!bloom-beacon.mit.edu!news.kodak.com!news-pen-16.sprintlink.net!newsfeed.nysernet.net!news.nysernet.net!207.41.200.14!news-pen-14.sprintlink.net!206.229.87.26!news-east.sprintlink.net!news-peer.sprintlink.net!news.sprintlink.net!Sprint!newsfeed.internetmci.com!131.103.1.114!news1.chicago.iagnet.net!qual.net!iagnet.net!newsspool.doit.wisc.edu!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: Tue, 27 Jan 1998 10:52:09 -0600 Organization: BioKin Consulting Lines: 16 Message-ID: <34CE10B9.32180EEE@biokin.com> References: <6akjlt$p9@mserv1.dl.ac.uk> NNTP-Posting-Host: a13-41.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Elisabeth Bull Daae wrote: > I would just like to add my name to the list of people who think this group > is worth continuing. So do I. As the previous writer indicated, if there is no activity for two months it's probably a blessing. It means that spam-senders and other electronic vermin have yet to discover 'bionet.metabolic-reg'! Really, looking at the last 10 messages, I only see -one- MEET YOUR MATCH ($2.99/min, 18Y OLD), but -no- TEENS WITH MEN HARDCORE. Let's keep this place a secret... :) _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: Thermodynamic potential of the ATP system (reply to Athel) Date: 27 Jan 1998 07:02:08 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 17 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <1326325161-243595274@ciit.org> NNTP-Posting-Host: net.bio.net Without going into an extensive treatment, it seems that this analysis ignores osmotic pressure, and assumes that the rate of A moving upward is exactly equal to the rate of B moving downward. The rate of movement will be proportional to the chemical activity difference across the two compartments. Finally, if the concentration of A is greater (than equilibrium) below, then some of that A will react to B in the lower compartment. In short, if you wrote down the set of differntial equations for this system, accounting for changes in osmotic pressure and the effect of that on chemical activities (not concentration), then you'd find that the whole will approach equilibrium with time, independent of the actual values of the rate constants. -Paul Schlosser From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!ATHE.WUSTL.EDU!toni From: toni@ATHE.WUSTL.EDU (Toni Kazic) Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 27 Jan 1998 11:51:22 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 10 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801271949.NAA06827@athe.wustl.edu> References: NNTP-Posting-Host: net.bio.net Paul, I have a vague idea that heterogeneous kinetics look quite a bit different from our regular solution-based kinetics. I've always presumed heterogeneous kinetics would apply in the situation you describe. Are you say they simply differ in the units? Or am I missing something? cheers, Toni From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!europa.clark.net!194.159.255.21!dispose.news.demon.net!demon!nntp.news.xara.net!xara.net!server5.netnews.ja.net!infoserv.aber.ac.uk!not-for-mail From: "Douglas B. Kell" Newsgroups: bionet.metabolic-reg Subject: Re: Heterogeneous kinetics Date: 27 Jan 1998 22:56:26 GMT Organization: University of Wales - Aberystwyth - Prifysgol Cymru Message-ID: <01bd2b76$b7c7c5a0$2b187c90@osfa.aber.ac.uk> References: <199801271949.NAA06827@athe.wustl.edu> NNTP-Posting-Host: pcbjgc.ras.aber.ac.uk X-Disclaimer: Warning - Sender not verified X-Newsreader: Microsoft Internet News 4.70.1155 Lines: 28 It's more interesting. If you assume (correctly) that the enzymes are NOT homogeneously distributed, A and B are small molecules and free, and E is an enzyme in the membrane, E is effectively immobile on the timescale of most common interest, but A and B can get to it one of 2 ways: by 3D diffusion from bulk to surface where they hit it 'directly', or by 3D diffusion to the "large" overall target surface followed by 2D diffusion ALONG the surface. It was first shown, in a slightly obscure but nonetheless classic paper (277 citations in the ISI database) by G. Adam & M. Delbrück (1968), in Structural Chemistry & Molecular Biology, ed. A.Rich, pp. [not to hand but cited properly in my 1979 BBA review 549, 55-99] that the 2D route tends to win hands down. (There are many implicit assumptions about unstirred layers &c that could be looked at in more detail.) Hans & I also discussed some of these issues apropos microcompartmentation of membrane energy coupling in e.g. Westerhoff, H.V., Kell, D.B., Kamp, F. & van Dam, K. (1988) The membranes involved in proton-mediated free-energy transduction: thermodynamic implications of their physical structure. In: Microcompartmentation (D.P. Jones, ed.) CRC Press, Boca Raton, pp. 115-154. Douglas. (Prof.) Douglas B. Kell, Cledwyn Building, Institute of Biological Sciences, University of Wales, Aberystwyth SY23 3DD Tel: +44 1970 622334 Fax: +44 1970 622354 dbk@aber.ac.uk http://gepasi.dbs.aber.ac.uk/home.htm From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!ATHE.WUSTL.EDU!toni From: toni@ATHE.WUSTL.EDU (Toni Kazic) Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 27 Jan 1998 13:31:34 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1 Sender: daemon@net.bio.net Distribution: world Message-ID: <199801272129.PAA07014@athe.wustl.edu> References: NNTP-Posting-Host: net.bio.net right, that makes sense, thanks From owner-metabolic-reg@net.bio.net Mon Jan 26 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 27 Jan 1998 12:22:38 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 27 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <199801271949.NAA06827@athe.wustl.edu> NNTP-Posting-Host: net.bio.net Toni, >I have a vague idea that heterogeneous kinetics look quite a bit >different from our regular solution-based kinetics. I've always >presumed heterogeneous kinetics would apply in the situation you >describe. Are you say they simply differ in the units? Or am I >missing something? I did leave out one potentially significant factor: diffusional limitation. If you have a catalyst particle, where much of the catalyst is in pores in the particle, then the time it takes for the substrate to get in becomes important. Even with the catalyst or enzyme on an exposed surface, if the reaction rate is on the order of or faster than the rate of diffusion, the kinetics also change. In the case where diffusional resistance is negligable (e.g., the fluid medium is well mixed, all the catalyst/enzyme is "exposed", the rate of reaction is much slower than the rate of diffusion) the kinetics are basically the same. In fact, many of the cellular enzymes we treat as "in solution" are contained in membranes, but we can readily treat them with the same math. -Paul From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!IR2CBM.CNRS-MRS.FR!athel From: athel@IR2CBM.CNRS-MRS.FR (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: Re: Shifted equilibrium of the catalysed reaction A + B <-> C? Date: 28 Jan 1998 10:06:58 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 23 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net >How about the equilibrium of the reaction A + B <-> C on adding the >catalyst? The forward reaction was diffusion-dependent and now it is in a >sense "more" diffusion-dependent. The back reaction was NOT >diffusion-dependent but now it is. Can we expect that the rate constants >change proportionally so that their ratio K = Kf/Kb remains the same? Yes, we must expect it: if the kinetics don't agree with thermodynamic necessity there is something wrong with the kinetic model. The only way a catalyst can change the position of an equilibrium is by being present at a high enough concentration to bind a significant proportion of the reactants, but then it's acting as a reactant and not as a catalyst, so this is not a counter-example. Athel Email: athel@ibsm.cnrs-mrs.fr Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/homepage.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!BGUMAIL.BGU.AC.IL!aflaloc From: aflaloc@BGUMAIL.BGU.AC.IL (claude aflalo) Newsgroups: bionet.metabolic-reg Subject: heterogeneous catalysis Date: 28 Jan 1998 05:38:44 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 87 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net On 27 Jan 1998, Paul M. Schlosser wrote: > Toni, > > >I have a vague idea that heterogeneous kinetics look quite a bit > >different from our regular solution-based kinetics. I've always > >presumed heterogeneous kinetics would apply in the situation you > >describe. Are you say they simply differ in the units? Or am I > >missing something? > > I did leave out one potentially significant factor: diffusional > limitation. If you have a catalyst particle, where much of the > catalyst is in pores in the particle, then the time it takes for the > substrate to get in becomes important. Even with the catalyst or > enzyme on an exposed surface, if the reaction rate is on the order > of or faster than the rate of diffusion, the kinetics also change. In this case the EFFECTIVE (observed) kinetic behavior will change not necessarily because of a change in INTRINSIC properties of the enzyme considered but primarily because of its special distibution, INHERENT to its being confined to a restricted compartment, different than bulk solution where the reactants concentration is calculated. In this case, in the relatively concentrated enzyme phase, due to fast catalysis there, the concentration of substrates and products at steady state are lower and higher, respectively, in comparison to these in bulk solution (where the substrates are added, and the products are normally measured). Now since the localized enzyme "senses" LOCAL substrate concentration, it behaves accordingly (slower rate at steady state, not only due to relatively lower substrate but sometimes to higher product concentrations, as well different pH, ionic strength or cofactor concentrations occuring locally). When bulk measurements are plotted against the concentration of reactants added to solution, the kinetic behavior of the enzyme looks different than that observed for the same solubilized enzyme (homogeneous catalysis). > In the case where diffusional resistance is negligable (e.g., the > fluid medium is well mixed, all the catalyst/enzyme is "exposed", > the rate of reaction is much slower than the rate of diffusion) the > kinetics are basically the same. Not necessarily. For small particles (e.g. mitochondria), this "well mixed" exhalted state cannot easily be achieved, even with the fastest magnetic stirrers. A rather comprehensive treatment of modeling heterogeneous catalysis in a coupled system (Ox Phos in mitochondria and hexokinase in solution) has been published, where the intermediate ATP was measured either in solution or at the surface of the membrane by native (soluble) or localized luciferase [Aflalo, C. and L.A. Segel, Local probes and heterogeneous catalysis: a case study of a mitochondria-luciferase-hexokinase coupled system. J. Theor. Biol., 1992. 158: p. 67-108]. The experimental aspects of that appear in [Aflalo, C., Localized firefly luciferase probes ATP at the surface of mitochondria. J. Bioenerg. Biomemb., 1997. 29(6): p. 549-559]. Diffusional restrictions were also reported in many other systems (e.g. [Aflalo, C. and N. Shavit, Steady-state kinetics of photophosphorylation: Limited access of nucleotides to the active site on the ATP synthetase. FEBS Lett, 1983. 154: p. 175-179. Aflalo, C. and N. Shavit, A new approach to the mechanism of photo- phosphorylation: modulation of ATP synthetase activity by limited diffusibility of nucleotides near the enzyme. Curr. Top. Cell. Regul., 1984. 24: p. 435-445]). > In fact, many of the cellular enzymes we treat as "in solution" are > contained in membranes, but we can readily treat them with the same > math. This may apply to EFFECTIVE behaviors which would yield EFFECTIVE kinetic parameters. The latter may represent only a vague estimate of the INTRINSIC parameters of the enzyme which are relevant to its mechanism. Only a combination of both provide useful information on the enzyme function and regulation in situ. Anyway both the mathematical treatment and the interpretation of bulk measurements are not always so readily easy and unequivocal (which often results in stochastic activity in this newsgroup...;-) > -Paul Sincerely, Claude Claude Aflalo ######################## Phones: Office 972-7-6472118 #### Dept. of Life Sciences Lab 972-7-6472119 Ben Gurion University of the Negev Fax 972-7-6472890 P.O.Box 653 email: aflaloc@bgumail.bgu.ac.il Beer Sheva 84105 Israel URL: http://www.bgu.ac.il/life/aflalo.html From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!agate!howland.erols.net!europa.clark.net!194.159.255.21!dispose.news.demon.net!demon!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Thermodynamic potential of the ATP system Date: 28 Jan 1998 11:33:48 -0000 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6an52s$fpj@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Lines: 49 I am sorry for disturbing the group again, but Paul's comments are very stimulating (at leat to me). Let me only answer him. Paul Schlosser wrote:>>>>>>>>>>> Without going into an extensive treatment, it seems that this analysis ignores osmotic pressure, and assumes that the rate of A moving upward is exactly equal to the rate of B moving downward. The rate of movement will be proportional to the chemical activity difference across the two compartments. Finally, if the concentration of A is greater (than equilibrium) below, then some of that A will react to B in the lower compartment. In short, if you wrote down the set of differntial equations for this system, accounting for changes in osmotic pressure and the effect of that on chemical activities (not concentration), then you'd find that the whole will approach equilibrium with time, independent of the actual values of the rate constants.<<<<<<<<<<<<<< You are right. So, in order to maintain the ATP system far from equilibrium, and if the chemiosmotic mechanism is used for this purpose, the energy required per mole is -(delta G), where delta G refers to ATP hydrolysis. This is universally accepted. However this is only the "restoring" part of the cycle that the ATP system undergoes. The "working" part is that in which ATP transfers energy to another system, e.g. drives the reaction B -> C (which could be some biopolymer synthesis): ATP + B -> ADP + P + C /1/ Thermodynamics says almost nothing about the work done by the ATP system in the non-equilibrium reaction /1/, but what could be rigorously proved is that this work is independent of the concentrations, e.g. of the ATP concentration. On the other hand, the delta G work does depend on the concentrations and approaches zero as their values approach the equilibrium ones. Therefore a cycle is possible in which the ATP system does some concentration- independent work Wi in /1/, then its initial (non-equilibrium) state is restored by a chemiosmotic mechanism and concentration-dependent (delta G) work Wd is spent, and the final balance is Wi > Wd. It seems to me that Wi - Wd is an extremely important quantity - it describes the net work done by the ATP system in biosynthetic processes for a given STEADY STATE of the ATP system. So I decided to call it "thermodynamic potential" and to offer it for discussion in this group (I do not see a more suitable one), but....... Best regards, Pentcho From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!agate!howland.erols.net!netnews.com!news.maxwell.syr.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Thermodynamic potential of the ATP system Date: 28 Jan 1998 11:24:06 -0000 Lines: 49 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6an4gm$far@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk I am sorry for disturbing the group again, but Paul's comments are very stimulating (at leat to me). Let me only answer him. Paul Schlosser wrote:>>>>>>>>>>> Without going into an extensive treatment, it seems that this analysis ignores osmotic pressure, and assumes that the rate of A moving upward is exactly equal to the rate of B moving downward. The rate of movement will be proportional to the chemical activity difference across the two compartments. Finally, if the concentration of A is greater (than equilibrium) below, then some of that A will react to B in the lower compartment. In short, if you wrote down the set of differntial equations for this system, accounting for changes in osmotic pressure and the effect of that on chemical activities (not concentration), then you'd find that the whole will approach equilibrium with time, independent of the actual values of the rate constants.<<<<<<<<<<<<<< You are right. So, in order to maintain the ATP system far from equilibrium, and if the chemiosmotic mechanism is used for this purpose, the energy required per mole is -(delta G), where delta G refers to ATP hydrolysis. This is universally accepted. However this is only the "restoring" part of the cycle that the ATP system undergoes. The "working" part is that in which ATP transfers energy to another system, e.g. drives the reaction B -> C (which could be some biopolymer synthesis): ATP + B -> ADP + P + C /1/ Thermodynamics says almost nothing about the work done by the ATP system in the non-equilibrium reaction /1/, but what could be rigorously proved is that this work is independent of the concentrations, e.g. of the ATP concentration. On the other hand, the delta G work does depend on the concentrations and approaches zero as their values approach the equilibrium ones. Therefore a cycle is possible in which the ATP system does some concentration- independent work Wi in /1/, then its initial (non-equilibrium) state is restored by a chemiosmotic mechanism and concentration-dependent (delta G) work Wd is spent, and the final balance is Wi > Wd. It seems to me that Wi - Wd is an extremely important quantity - it describes the net work done by the ATP system in biosynthetic processes for a given STEADY STATE of the ATP system. So I decided to call it "thermodynamic potential" and to offer it for discussion in this group (I do not see a more suitable one), but....... Best regards, Pentcho From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!newsfeed.direct.ca!news.he.net!news.pagesat.net!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: Tue, 27 Jan 1998 23:48:58 -0600 Organization: BioKin Consulting Lines: 26 Message-ID: <34CEC6CA.3A3C43A2@biokin.com> References: <199801271949.NAA06827@athe.wustl.edu> NNTP-Posting-Host: a13-41.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Paul M. Schlosser wrote: [...] > In fact, many of the cellular enzymes we treat as "in solution" are > contained in membranes, but we can readily treat them with the same > math. Not always... See Nelsestuen, G.L., & Martinez, M.B. (1997) "Steady State Enzyme Velocities That Are Independent of [Enzyme]: An Important Behavior in Many Membrane and Particle-Bound States" Biochemistry 36 (30) 9081-9086. However, I would like to know what people think about the nonlinear Eadie-Hofstee plot in Figure 1B, on which a lot of the discussion seems to depend... Haven't we all seen similar 'deviant' plots for many different reasons, including the presence of impurities in substrate(s)? Petr _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 28 Jan 1998 08:57:18 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 28 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <1326135117-255025920@ciit.org> NNTP-Posting-Host: net.bio.net >From: kohn@valiant.niehs.nih.gov ("Michael Kohn") >Subject: Re: heterogeneous catalysis >I encounter similar cases in my own work involving metabolism of xenobiotics >by inducible enzymes bound to the hepatic endoplasmic reticulum. Olefinic >chemicals are oxidized by several isoforms of cytochrome P450 to epoxides, >which are converted to vicinal diols by the microsomal enzyme epoxide >hydrolase. The net rate of accumulation of the epoxide intermediate cannot >be reproduced by equations that treat these two enzymes as independent. >Hydrolysis of an endogenously produced epoxide is more rapid than observed >when"preformed" epoxide (not its precursor) is the exogenously supplied >substrate. .... Michael, I'm sure that you are also aware of the issue of spacial enzyme localization within the hepatic acinus, which appears to explain the "preferential" conversion of endogenously formed phenol to hydroquinone, vs. the higher sulfation of exogenously administered phenol. Even if EH is distributed uniformly in the liver, the centilobular localization of P450 can give the appearance of channeling but can be described adequately by treating the liver as a series of well-mixed compartments in series, corresponding to the different zones of the acinus. Has this been rulled out for olefins? -Paul From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!VALIANT.NIEHS.NIH.GOV!kohn From: kohn@VALIANT.NIEHS.NIH.GOV ("Michael Kohn") Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 28 Jan 1998 08:30:08 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 46 Sender: daemon@net.bio.net Distribution: world Message-ID: <9801281121.ZM24920@valiant.niehs.nih.gov> NNTP-Posting-Host: net.bio.net The rates of reactions catalyzed by immoblized enzymes has been a subject of concern for decades. As pointed out by Paul Schlosser, Douglas Kell, et al. restricted diffusion to the site of the enzyme alters the local concentration of substrate in an "unstirred layer." But there is another interesting component; enzymes in a pathway may be membrane bound with adjacent proteins catalyzing sequential steps. The most common example is in mitochondria, but it was reported by an Australina lab in Biochemical Journal (I think) for muscle contractile filaments about 20 years ago. The glycolytic enzymes plus malate dehydrogenase line up along actin filaments. So NADH formed at glyceraldehyde phosphate dehydrogenase, for example, is reoxidized by lactate dehydrogenase and malate dehydrogenase localized nearby on the filament. Such "privileged access" or "channeling" of substrates has been the focus of much research in recent years. I encounter similar cases in my own work involving metabolism of xenobiotics by inducible enzymes bound to the hepatic endoplasmic reticulum. Olefinic chemicals are oxidized by several isoforms of cytochrome P450 to epoxides, which are converted to vicinal diols by the microsomal enzyme epoxide hydrolase. The net rate of accumulation of the epoxide intermediate cannot be reproduced by equations that treat these two enzymes as independent. Hydrolysis of an endogenously produced epoxide is more rapid than observed when "preformed" epoxide (not its precursor) is the exogenously supplied substrate. Johannes Filser in Germany treats this endogenous epoxide intermediate as localized in a hypothetical subcellular compartment. I follow Douglas Kell's idea of an intermediate which diffuses laterally along the endoplasmic reticulum membrane faster than it diffuses into the bulk cytoplasm and therefore encounters the hydrolase faster than it would if exogenously supplied. -- Michael C. Kohn Laboratory of Computational Biology and Risk Analysis National Institute of Environmental Health Sciences P.O. Box 12233, Mail Drop A3-06 Research Triangle Park, NC 27709-2233 Telephone: 919-541-4929 (voice) 919-541-1479 (fax) e-mail: kohn@valiant.niehs.nih.gov WWW home page: http://valiant.niehs.nih.gov From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!agate!newsfeed.kornet.nm.kr!nntp.kreonet.re.kr!news.maxwell.syr.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Shifted equilibrium of the catalysed reaction A + B <-> C? Date: 28 Jan 1998 15:51:17 -0000 Lines: 21 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6ank5l$ql@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Herbert Sauro wrote:>>>>>>>>>>> I don't have easy access to University libraries etc because if I did I could probably look it up but my question concerns membrane transport kinetics. In a mixed solution containing two components, A and B and an enzyme which can convert A + B to C, the rate at which the enzyme complex EAB forms is proportional to E*A*B - I hope I've got that bit right. I presume this comes from considerations of collision probabilities in a perfectly mixed compartment. What I want to know is what would happen if the enzyme were stuck on a membrane, i.e confined to a 2D surface but with the substrates, A + B still mixed in the bulk solution. What would be the rate of formation of EAB be proportional too? Would it be the same (i.e E*A*B) or different because one of the colliding particles (E) can no longer freely diffuse in 3D?<<<<<<<< How about the equilibrium of the reaction A + B <-> C on adding the catalyst? The forward reaction was diffusion-dependent and now it is in a sense "more" diffusion-dependent. The back reaction was NOT diffusion- dependent but now it is. Can we expect that the rate constants change proportionally so that their ratio K = Kf/Kb remains the same? Pentcho From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 28 Jan 1998 07:35:05 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 62 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net >Now since the localized enzyme "senses" LOCAL substrate concentration, >it behaves accordingly (slower rate at steady state, not only due to >relatively lower substrate but sometimes to higher product >concentrations, as well different pH, ionic strength or cofactor >concentrations occuring locally). In chemical engineering the ratio: actual rate ------------------------------------------------------ rate that would occur without mass transfer resistance is referred to as an effectiveness factor. It is (by definition) less than one, since there will always be some resistance. But it can be very close to one. >When bulk measurements are plotted >against the concentration of reactants added to solution, the kinetic >behavior of the enzyme looks different than that observed for the same >solubilized enzyme (homogeneous catalysis). This may also be due to the fact that being in a membrane holds the enzyme in a particular orientation--so that a collision with a substrate molecule is more likely to result in binding--and/or changes in enzyme conformation due to being (mostly) in a lipid vs. an aqueous environment (protection against denaturation included). One can easily estimate the diffusivity of small molecules and compare this to the actual rate of the reaction (along with an appropriate diffusional distance, like the diameter of a cell) to see if diffusion is playing much of a role. Tortuosity of the path required for a substrate molecule to reach the enzyme adds to diffusional resistance. >This may apply to EFFECTIVE behaviors which would yield EFFECTIVE kinetic >parameters. The latter may represent only a vague estimate of the >INTRINSIC parameters of the enzyme which are relevant to its mechanism. I.e, the effectiveness factor is lumped in with the kinetics. But the original question asked if you needed to use different equations (i.e., if the rate becomes independent of [enzyme]). Given some of the factors mentioned above (especially conformational changes), I suggest that it is very difficult to measure an enzyme's intrinsic properties (in the environment of the membrane), though the references given by Claude show that it can be done. More often, one is stuck with fitting effective parameters to data which include whatever diffusional resistance exists. Which brings us back to the question: what equation should be used? I'd still suggest using the same equation as for bulk solution as a first attempt, and only turning to more complex analyses which include diffusional resistance if that fails. At the other extreme, the rate can be almost entirely diffusion-limited (and hence independent of [enzyme]) which may be the case in Peter Kuzmic's citation. But I don't think that is common. -Paul From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!europa.clark.net!204.59.152.222!news-peer.gip.net!news.gsl.net!gip.net!newspump.sol.net!sol.net!news.pagesat.net!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: Shifted equilibrium of the catalysed reaction A + B <-> C? Date: Wed, 28 Jan 1998 12:51:27 -0600 Organization: BioKin Consulting Lines: 49 Message-ID: <34CF7E2F.B4EDEA77@biokin.com> References: NNTP-Posting-Host: a3-27.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Athel Cornish-Bowden wrote: > > [...] Can we expect that the rate constants > >change proportionally so that their ratio K = Kf/Kb remains the same? > > Yes, we must expect it: if the kinetics don't agree with thermodynamic > necessity there is something wrong with the kinetic model. Perhaps a semantic footnote might be appropriate here. I submit that the rate constants k+ and k- in k+ A + B <==> C /1/ k- do not "change" at all merely upon adding a catalyst, which causes an entirely different sequence of steps to occur, for example (in the case of an enzyme following the ordered 'bi-uni' mechanism) k1 A + E <==> EA /2/ k2 k3 EA + B <==> EAB /3/ k4 k5 EAB <==> EC /4/ k6 k7 EC <==> E + C /5/ k8 so that the complete reaction mechanism now consists of reactions /1/ - /5/. The rate constants k+, k- that describe the uncatalyzed process (true to their designation as 'constants') can change only with temperature, pressure, or other physical factors, but not by the presence of a catalyst. Petr _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!news-peer.gip.net!news.gsl.net!gip.net!portc01.blue.aol.com!audrey01.news.aol.com!not-for-mail From: nickbioman@aol.com (NickBioMan) Newsgroups: bionet.metabolic-reg Subject: Re: This group doesn't seem to get much attention Date: 28 Jan 1998 23:03:03 GMT Lines: 13 Message-ID: <19980128230301.SAA13846@ladder03.news.aol.com> NNTP-Posting-Host: ladder03.news.aol.com X-Admin: news@aol.com References: <34CCE9B1.3FBE3FD0@ibex.ca> Organization: AOL, http://www.aol.co.uk X-Newsreader: AOL Offline Reader Oh yes this group must keep going. I am new to the net and only discovered this group after sitting my metabolic integration exam in January. As a final year Biochemistry student I shall be a frequent vistor here - looking for help no doubt! Keep talking Nick B Student Nick Ball Student at Nescot From owner-metabolic-reg@net.bio.net Tue Jan 27 22:00:00 1998 Path: biosci!VALIANT.NIEHS.NIH.GOV!kohn From: kohn@VALIANT.NIEHS.NIH.GOV ("Michael Kohn") Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 28 Jan 1998 10:23:38 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 49 Sender: daemon@net.bio.net Distribution: world Message-ID: <9801281314.ZM25368@valiant.niehs.nih.gov> NNTP-Posting-Host: net.bio.net On Jan 28, 8:57am, Paul M. Schlosser wrote: > Michael, > > I'm sure that you are also aware of the issue of spacial enzyme localization > within the hepatic acinus, which appears to explain the "preferential" > conversion of endogenously formed phenol to hydroquinone, vs. the higher > sulfation of exogenously administered phenol. Even if EH is distributed > uniformly in the liver, the centilobular localization of P450 can give the > appearance of channeling but can be described adequately by treating the > liver as a series of well-mixed compartments in series, corresponding to > the different zones of the acinus. Has this been rulled out for olefins? >-- End of excerpt from Paul M. Schlosser Paul, Yes, I'm aware of the elegant modeling Elaina Kenyon did with benzene metabolism showing how the relative amounts of phenol and hydroquinone produced could be understood by localization of the enzymes in different cells. I never heard of such localization for epoxide hydrolase. The epoxide problem is the reverse, anyway. A model which has free access to all enzymes overpredicts the amount of epoxide secreted into the blood. If the olefin were oxidized in centrilobular cells, the epoxide intermediate secreted into the sinusoids near the central vein, and the epoxide absorbed by periportal cells at the beginning of the sinusoid on the next pass of the blood through the liver, we'd expect more epoxide in the blood than predicted by independent enzyme models not less as is actually observed. We must find a mechanism that shields the intermediate from exchange with the extracellular space. Both subcellular compartmentation and privileged access solve this problem, but I'm not aware of any direct evidence supporting either one. Michael -- Michael C. Kohn Laboratory of Computational Biology and Risk Analysis National Institute of Environmental Health Sciences P.O. Box 12233, Mail Drop A3-06 Research Triangle Park, NC 27709-2233 Telephone: 919-541-4929 (voice) 919-541-1479 (fax) e-mail: kohn@valiant.niehs.nih.gov WWW home page: http://valiant.niehs.nih.gov From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!BGUMAIL.BGU.AC.IL!aflaloc From: aflaloc@BGUMAIL.BGU.AC.IL (claude aflalo) Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 29 Jan 1998 00:00:27 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 69 Sender: daemon@net.bio.net Distribution: world Message-ID: References: Reply-To: claude aflalo NNTP-Posting-Host: net.bio.net On 28 Jan 1998, Paul M. Schlosser wrote: > >Now since the localized enzyme "senses" LOCAL substrate concentration, > >it behaves accordingly (slower rate at steady state, not only due to > >relatively lower substrate but sometimes to higher product > >concentrations, as well different pH, ionic strength or cofactor > >concentrations occuring locally). > > In chemical engineering the ratio: > > > actual rate > ------------------------------------------------------ > rate that would occur without mass transfer resistance > > > is referred to as an effectiveness factor. It is (by definition) less > than one, since there will always be some resistance. But it can be very > close to one. Right, but the difficult part is to get an expression of the effectiveness factor in terms of the intrinsic parameters of the enzyme (e.g., kcat, Km), its inherent parameters (surface or local concentration, dimensions of the support), and the mass transfer parameters (Diffusion coeff., stirring/flow, etc.). My paper in JTB 1992 provides that (eqs. 30-33) as well as its dependence on effective parameters ([total enzymes]). It is also shown (assuming identical intrinsic kinetic parameters for the localized and soluble enzyme) that this effectiveness factor represents the ratio of average product concentration to local product concentration. The bottom line is that in a moderately slow reconstituted biological system (mitochondria even in plain aqueous suspension) the diffusional restrictions are most significant, as seen by a local observer. The conclusion, as pointed out by Michael Kohn, is that there is a marked advantage for enzymes catalyzing sequential steps to be colocalized. Moreover, spatial segregation of different isozymes even within the same topological compartment (e.g., the so-called cytosol or even mitochondrial matrix) may lead to distinct different metabolic paths for the same metabolite in this compartment. > More often, one is stuck with fitting effective parameters to data which > include whatever diffusional resistance exists. Which brings us back to > the question: what equation should be used? I'd still suggest using the > same equation as for bulk solution as a first attempt, and only turning > to more complex analyses which include diffusional resistance if that > fails. The point is that fitting effective behaviors to homogeneous catalysis equations never fails! (at least if one is not too fussy about perfect fit). I would say that a proper diagnosis of diffusional resistances is always pertinent. A simple experimental test is measurements +/- stirring (in the case of particles the size of yeast and above), but as pointed out above, one can be surprised... Who said there's no "action" in this group? Claude Claude Aflalo ######################## Phones: Office 972-7-6472118 #### Dept. of Life Sciences Lab 972-7-6472119 Ben Gurion University of the Negev Fax 972-7-6472890 P.O.Box 653 email: aflaloc@bgumail.bgu.ac.il Beer Sheva 84105 Israel URL: http://www.bgu.ac.il/life/aflalo.html From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!agate!newsgate.duke.edu!news.ysu.edu!Cabal.CESspool!bofh.vszbr.cz!news.maxwell.syr.edu!news.he.net!news.pagesat.net!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: Shifted equilibrium (reply to Petr Kuzmic) Date: Thu, 29 Jan 1998 13:49:54 -0600 Organization: BioKin Consulting Lines: 50 Message-ID: <34D0DD62.D5694D70@biokin.com> References: <6aqhv8$ot5@mserv1.dl.ac.uk> NNTP-Posting-Host: a3-27.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Pentcho Valev: -------------- (k+_catalyzed)/(k+) = (k8)(E)/(k-) /6/ I am not sure that /6/ is unproblematic. Petr Kuzmic: ------------ We'll be in a better position to answer that, as soon as you (1) define k+_catalyzed. Pentcho Valev: -------------- At the moment I am a bit lazy [...]. Paul Schlosser started deriving something like that recently - I assume it is not difficult. Petr Kuzmic: ----------- No, it is not difficult indeed. The formal treatment of the 'specificity number' (which is your k+[catalyzed]) is containd in any introductory textbook on enzyme kinetics. Pentcho Valev: -------------- > Petr, again no scientific probem seems to exist - only my wicked nature > is exposed. I am rather used to it, but still....why? Petr Kuzmic: ------------ Really, "...why"? Something to think about... But I never you are wicked, I said something about a 'dilettante'. 'Dilettante' is almost synonymous with 'amateur', a kindly epithete in my mind. For your convenience I'll quote my Webster's dictionary: "DILETTANTE [dilettare = to take delight in] One who follows a branch of knowledge desultorily or superficially, or as a pastime." "DESULTORY [desultorius = one who leaps] Jumping, or passing, from one thing or subject to another, without order or rational connection." Think about it. Read one of Athel's books on kinetics, they are short and sweet. Than think again. Than post. --Petr From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Excuse Date: 29 Jan 1998 19:01:00 -0000 Lines: 5 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aqjlc$qhg@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk I am sorry - Petr Kuzmic sent me a "kind" message but it was private - I did not realise that and replied to the group. Please ignore this reply. Pentcho From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Shifted equilibrium (reply to Petr Kuzmic) Date: 29 Jan 1998 18:32:08 -0000 Lines: 4 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aqhv8$ot5@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Petr, again no scientific probem seems to exist - only my wicked nature is exposed. I am rather used to it, but still....why? Pentcho From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!newsfeed.direct.ca!news2.chicago.iagnet.net!qual.net!iagnet.net!144.92.88.12!newsspool.doit.wisc.edu!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: Reformulation of the 2nd law in kinetic terms Date: Thu, 29 Jan 1998 11:50:14 -0600 Organization: BioKin Consulting Lines: 56 Message-ID: <34D0C156.5378CB4F@biokin.com> References: <6aqdel$k8v@mserv1.dl.ac.uk> NNTP-Posting-Host: a3-27.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) Pentcho Valev wrote: > In fact, the second law in this case takes the > following form: > > (k+_catalyzed)/(k+) = (k-_catalyzed)/(k-) /7/ > > By comparing /6/ and /7/ we see that > > k-_catalyzed = k8(E) /8/ This definition of "k-(catalyzed)" cannot stand. To understand why, write the original reaction as k+ C <===> A + B /1'/ k- and try your definitions on it. Compare results with your formal treatment of k+ A + B <===> C /1/ k- The results must be invariant. > At the moment I am a bit lazy [...], but k+_catalyzed should satisfy > the equation > > Vforward = (k+_catalyzed)(A)(B) /9/ Not true. In that case k+(catalyzed) is not a constant, because V[forward] depends also on the concentration of the enzyme (no matter how small it is, in particular, negligibly small compared with [A], [B], [C]). > Paul Schlosser started deriving something like that > recently - I assume it is not difficult. No, it is not difficult indeed. The formal treatment of the 'specificity number' (which is your k+[catalyzed]) is containd in any introductory textbook on enzyme kinetics. (Please note that our frequent correspondent Athel Cornish-Bowden is in the Guiness Book of Records for the largest number of introductory textbooks with "Enzyme Kinetics" in the title). I admit it: in asking you to define k+[catalyzed] I was trying to see if an iquisitive dilettante could briskly arrive at the 'specificity number' from first principles... I guess I failed: the human propensity for laziness prevailed again... :) --Petr _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Reformulation of the 2nd law in kinetic terms Date: 29 Jan 1998 17:15:01 -0000 Lines: 36 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aqdel$k8v@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk I wrote:>>>>>>>>>>>>>>> > Let us > try to determine the substitute for k+ for the catalyzed process: if it is > k+_catalyzed, we can reformulate the second law in kinetic terms: > > (k+_catalyzed)/(k+) = (k8)(E)/(k-) /6/ > > I am not sure that /6/ is unproblematic.<<<<<<<<<<<<<<<<<< Petr Kuzmic replied:>>>>>>>>>>>> We'll be in a better position to answer that, as soon as you (1) define k+_catalyzed, and (2) explain why is there no k-_catalyzed in your formalism.<<<<<<<<<<<< There is k-_catalized. In fact, the second law in this case takes the following form: (k+_catalyzed)/(k+) = (k-_catalyzed)/(k-) /7/ By comparing /6/ and /7/ we see that k-_catalyzed = k8(E) /8/ where k8 comes from your analysis. At the moment I am a bit lazy and have difficulties in shifting from thermodynamic to kinetic calculations, but k+_catalyzed should satisfy the equation Vforward = (k+_catalyzed)(A)(B) /9/ and should be a finction of the constants you introduced and the enzyme concentration. Paul Schlosser started deriving something like that recently - I assume it is not difficult. Pentcho From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!bloom-beacon.mit.edu!news.kodak.com!news-pen-16.sprintlink.net!newsfeed.nysernet.net!news.nysernet.net!207.41.200.14!news-pen-14.sprintlink.net!206.229.87.26!news-east.sprintlink.net!news-peer.sprintlink.net!news.sprintlink.net!Sprint!news-peer.gip.net!news-lond.gip.net!news.gsl.net!gip.net!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: athel@ir2cbm.cnrs-mrs.fr (Athel Cornish-Bowden) Newsgroups: bionet.metabolic-reg Subject: Re: No action? Date: 29 Jan 1998 17:14:30 -0000 Lines: 48 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aqddm$k74@mserv1.dl.ac.uk> X-Sender: cornish@ibsm.cnrs-mrs.fr Original-To: btk-mca@dl.ac.uk Petr Kuzmic wrote: >Athel Cornish-Bowden wrote: >> While I sympathize with the >> people who said it doesn't really matter if the group is moribund for a >> period and then springs into life again I think they are mistaken. >That could be a reference to my saying "let's keep this place a secret" a >few days ago. I should clarify that this was an (apparently too feeble) >attempt at humor [I admit it: sarcasm]. No, it wasn't. (As with virtually all of your postings, I found nothing to disagree with, and I realized this was written with your tongue in your cheek (as of course was my original suggestion to let the group die a natural death: the aim was to get some of the secret btk-mca'ers to come out of the closet)) I was more thinking of Elisabeth Bull Dae's comment that >It is actually good that we don't have to much activity, because when you >get a mail from this group once in a while you actually read it. If it was >long postings every day, it would quickly become overwhelming and it would >not be time to read all of it. Quality is always better than quantity! and I think there were others similar. I don't have the impression that these were intended humorously. What I meant was that while I understand Elisabeth's opinion I think a group cannot survive letting its level of activity fall too low. Look at the AMYLOID group, for example, which serves people interested in Alzheimer's. In January 1998 it has had a total of zero messages posted. Does this mean that there aren't any researchers interested in Alzheimer's? No, it surely means that the level of activity has fallen so low that such people go somewhere else to exchange views. The AMYLOID group is moderated, but a similar case that is not moderated is JRNLNOTE. This had a ragbag of around ten postings in January, of which one is more or less serious but not relevant to the group, and the others are spam. (They don't even have a miniFAQ and Fundraiser to keep them amused). Athel Email: athel@ibsm.cnrs-mrs.fr Site map: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/sitemap.htm MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.htm MCA chapter from my book: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcai.htm From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!agate!logbridge.uoregon.edu!news-peer.gip.net!news-lond.gip.net!news.gsl.net!gip.net!baron.netcom.net.uk!netcom.net.uk!nntp.news.xara.net!xara.net!server5.netnews.ja.net!daresbury!not-for-mail From: Pentcho Valev Newsgroups: bionet.metabolic-reg Subject: Diffusion-controlled reactions Date: 29 Jan 1998 15:32:53 -0000 Lines: 17 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <6aq7f5$dao@mserv1.dl.ac.uk> Original-To: btk-mca@dl.ac.uk Guy Brown wrote:>>>>>>>>>>>>>> Why is it that if a reaction has a second order rate constant of anything from 10^7 to 10^12 (s^-1) it is described as "diffusion controlled"? Surely if collisions can occur at 10^12 then a rate constant of 10^7 can not be diffusion controlled. Presumably steric factors are invoked: the molecules collide without reacting. But how can we distinguish steric factors from the "binding" of the substrate by the enzyme? How low could a rate constant go and still be diffusion controlled?<<<<<<<<<<<<<<<<<< I am not competent, but here is a suggestion: not steric factors are essential but rather the effectiveness of conversion of ES into E + Product. In the limit it is absolutely effective so the concentration of ES is zero and the Michaelis-Menten curve is linear everywhere. Pentcho From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!agate!newsgate.duke.edu!news.vt.edu!solaris.cc.vt.edu!fci-se!fci!newsfeed.direct.ca!news.he.net!news.pagesat.net!news.itis.com!not-for-mail From: Petr Kuzmic Newsgroups: bionet.metabolic-reg Subject: Re: Shifted equilibrium Date: Thu, 29 Jan 1998 09:08:10 -0600 Organization: BioKin Consulting Lines: 19 Message-ID: <34D09B5A.3E6BA788@biokin.com> References: <6ape3c$jd5@mserv1.dl.ac.uk> NNTP-Posting-Host: a3-27.itis.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 4.01 [en] (Win95; I) X-Priority: 3 (Normal) > Let us > try to determine the substitute for k+ for the catalyzed process: if it is > k+_catalyzed, we can reformulate the second law in kinetic terms: > > (k+_catalyzed)/(k+) = (k8)(E)/(k-) /6/ > > I am not sure that /6/ is unproblematic. We'll be in a better position to answer that, as soon as you (1) define k+_catalyzed, and (2) explain why is there no k-_catalyzed in your formalism. --Petr _____________________________________________________________ Petr Kuzmic Ph.D. * BioKin Ltd. * Madison, WI 53708-8336, USA pkuzmic@biokin.com * http://www.biokin.com * 608.256.1269 fax From owner-metabolic-reg@net.bio.net Wed Jan 28 22:00:00 1998 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org ("Paul M. Schlosser") Newsgroups: bionet.metabolic-reg Subject: Re: heterogeneous catalysis Date: 29 Jan 1998 07:17:17 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 58 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net >From: claude aflalo >It is also shown (assuming identical intrinsic kinetic parameters >for the localized and soluble enzyme) ... From discussions I have held with colleagues here, I have the impression that this is a rather questionable assumption. Then again, the belief that intrinsic properties can change with the local environment may have arisen from having presumed that diffusional resistance is negligable. A way to address this dilemma would be to calculate an effectiveness factor based on "intrinsic" (soluble) parameters and observed kinetics in a localized environment. Given the diffusivity of the substrate, one can then determine what diffusion path-length is required to give rise to that effectiveness. If this path-length is much larger (ie, orders of magnitude) than the scale of the system, then I'd conclude that some other factor must be causative. If memory serves, though, there are cases wh